Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Vorinostat and Isotretinoin in Treating Patients With Advanced Kidney Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Biomarker/Laboratory analysis, Treatment Active 21 and over NCI NYWCCC-0511008257 6896, NCI-6896, NCT00324740

Objectives

Primary

1. Determine the maximum tolerated dose and phase II dose of isotretinoin when given in combination with vorinostat (SAHA) in patients with advanced renal cell carcinoma. (Phase I)
2. Define dose-limiting and other toxicities in patients treated with this regimen. (Phase I)
3. Determine the objective response rate of patients treated with this regimen. (Phase II)

Secondary

1. Conduct a pharmacokinetic analysis of this regimen in these patients. (Phase I)
2. Conduct gene profiling analysis of pre-study, paraffin-embedded tissues from patients treated with this regimen. (Phase I)
3. Conduct correlative studies to identify the effect of SAHA and isotretinoin on RAR-B, LRAT, and STAT1-3 expression. (Phase I)

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed renal cell carcinoma
  • Advanced or metastatic disease



• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion > 20 mm by conventional techniques or > 10 mm by spiral CT scan (phase II only)



• Failed ≥ 2 prior treatment regimens, including chemotherapy, immunotherapy (i.e., interleukin or interferon), biological agents (i.e., kinase inhibitors), or combinations thereof
  • An overlap between classes of therapies given concurrently will be counted as 2 prior treatment regimens



• No known brain metastases

Prior/Concurrent Therapy:

• See Disease Characteristics
• Recovered from prior therapy
• At least 2 weeks since prior valproic acid or any other histone deacetylase inhibitor
• At least 4 weeks since prior radiotherapy
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
• At least 6 weeks since prior chemoimmunotherapy
• No concurrent antiretroviral therapy for HIV-positive patients
• No other concurrent anticancer therapy, including radiation, biologic, or chemotherapeutic agents, for renal cell carcinoma or other tumors
• No other concurrent investigational agents, valproic acid, or other retinoid

Patient Characteristics:

• ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
• Life expectancy > 3 months
• WBC ≥ 3,000/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Bilirubin ≤ 1.5 mg/dL
• AST and ALT < 2.5 times upper limit of normal
• Creatinine ≤ 2 mg/dL OR creatinine clearance > 50 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective double-method contraception for 1 month before, during, and for 1 month after completion of study treatment
• No history of allergic reactions or hypersensitivity attributed to compounds of similar chemical or biologic composition to vorinostat (SAHA), isotretinoin, or other agents or componenets (e.g., parabens) used in this study
• No uncontrolled intercurrent illness, including, but not limited to, any of the following:
  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness or social situation that would preclude study compliance

Expected Enrollment

A total of 50 patients will be accrued for this study.

Outcomes

Dose-limiting toxicities
Maximum tolerated dose
Objective response rate

Pharmacokinetics

Outline

This is a multicenter, phase I, dose-escalation study of isotretinoin, followed by a multicenter, phase II, prospective, non-randomized study.

• Phase I: Patients receive oral vorinostat (SAHA) twice daily and oral isotretinoin twice daily on days 3-5, 10-12, 17-19, and 24-26. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

  Cohorts of 3-6 patients receive escalating doses of isotretinoin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.




• Phase II: Patients receive SAHA as in phase I and isotretinoin as in phase I at the MTD determined in phase I.

Tissue and blood samples are obtained for biomarker/laboratory studies in weeks 1 and 4. Gene profile analysis is conducted on tumor tissue.

After completion of study treatment, patients are followed for 12 weeks.

Trial Contact Information

Trial Lead Organizations

New York Weill Cornell Cancer Center at Cornell University

David Nanus, MD, Protocol chair		Ph: 212-746-2920 Email: dnanus@med.cornell.edu

U.S.A.
New York
	Bronx
	Albert Einstein Cancer Center at Albert Einstein College of Medicine
		Clinical Trials Office - Albert Einstein Cancer Center at Albert Einstein College of Medicine	Ph:  718-904-2730
			Email: aecc@aecom.yu.edu
	New York
	Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
		Clinical Trials Office - Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center	Ph:  212-305-8615
	Mount Sinai Medical Center
		Max Sung, MD	Ph:  212-241-7902
			Email: max.sung@mssm.edu
	New York Weill Cornell Cancer Center at Cornell University
		Clinical Trials Office - New York Weill Cornell Cancer Center at Cornell University	Ph:  212-746-1848
	NYU Cancer Institute at New York University Medical Center
		Anna Ferrari, MD	Ph:  212-731-5389
			Email: anna.ferrari@nyumc.org

Registry Information
Official Title		A Phase I/II Study of Vorinostat (Suberoylanilide Hydroxamic Acid, SAHA) in Combination with Isotretinoin (13-cis Retinoic Acid, 13-CRA) in the Treatment of Patients with Advanced Renal Cell Carcinoma
Trial Start Date		2006-03-15
Trial Completion Date		2007-03-25 (estimated)
Registered in ClinicalTrials.gov		NCT00324740
Date Submitted to PDQ		2006-03-07
Information Last Verified		2008-04-27
NCI Grant/Contract Number		CM17103, CM62204